The major objectives of the research proposed in this application are: 1. to examine electrophysiological indices of cerebral asymmetry in subjects with several subtypes of depressive disorder and in bipolar patients when symptomatic and during remission; and 2. to determine whether resting measures of frontal and anterior temporal activation asymmetry predict vulnerability to drepressive disorders in a large unselected sample followed longitudinally for four years. In one experiment, Major Depressives and controls will be assessed initially on EEG measures of regional activation during rest and in response to short emotional film clips designed to elicit different discrete emotions. Self-report measures of emotional responsivity and measures of facial expressions of emotion will also be obtained in response to the film clips. Following this initial session, subjects will be tested at weekly intervals on resting measures of asymmetry and at an 8 and 16 week time point on EEG and behavioral responses to the film clips. Relations between changes in symptomatology over the course of the study and patterns of regional brain asymmetry at rest and in response to affective challenge will be examined. A second experiment calls for the study of depressive subtypes. Endogenous Major Depressives, Non-endogenous Major Depressives, Biploar depressed and Intermittent Depressed subjects will be tested in an experiment which examines resting EEG, EEG in response to emotional film clips and EEG in response to verbal and spatial cognitive tasks. Subjects will be tested at two points--when acutely depressed and 16 weeks later. The final experiment calls for the initial assessment of 300 unselected subjects on measures of resting activation asymmetry. Those falling at the upper and lower extremes, and those at the mid-point of the distribution on measures of frontal and anterior temporal asymmetry will be followed for four years. A diathesis/stress model of anterior activation asymmetries is proposed which argues that right-sided frontal and/or anterior temporal activation is assoicated with increased vulnerability to depressive symptomatology. Accordingly, depressive symptomatology in the extreme asymmetry groups will be assessed over the course of the study. Overall, the research proposed will advance our understanding of cerebral asymmetries related to depression and will provide important new information on the use of electrophysiological measures of regional activation asymmetries as markers of vulnerability to depressive disorders.